thesis on cardiac arrhythmia

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Overview of cardiac arrhythmias and treatment strategies.

1. Introduction

2. general principles, 2.1. genetics, 2.2. myocardial ischemia, 2.3. inflammation, 2.4. diet and metabolic disorders, 3. pharmacotherapy, 4. non-pharmacologic interventions, 4.1. implantable devices, 4.2. catheter ablation, 4.3. ischemic conditioning, 5. perspectives, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Kingma, J.; Simard, C.; Drolet, B. Overview of Cardiac Arrhythmias and Treatment Strategies. Pharmaceuticals 2023 , 16 , 844. https://doi.org/10.3390/ph16060844

Kingma J, Simard C, Drolet B. Overview of Cardiac Arrhythmias and Treatment Strategies. Pharmaceuticals . 2023; 16(6):844. https://doi.org/10.3390/ph16060844

Kingma, John, Chantale Simard, and Benoît Drolet. 2023. "Overview of Cardiac Arrhythmias and Treatment Strategies" Pharmaceuticals 16, no. 6: 844. https://doi.org/10.3390/ph16060844

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Arrhythmias Research

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As part of its broader commitment to research on heart diseases, the NHLBI leads and supports research and programs on different types of arrhythmia, or irregular heartbeat. The research we fund has helped develop and test several treatment options for arrhythmias. Current studies are looking a improving the diagnosis, prevention, and treatment for arrhythmias, which includes using artificial intelligence technologies and understanding how our genes can raise the risk of arrhythmia.

NHLBI research that really made a difference

• Safety and effectiveness of treatment: The NHLBI began the landmark Cardiac Arrhythmia Suppression Trial in 1986. The study tested whether a particular class of drugs to treat arrhythmias could prevent sudden cardiac arrest in people who had asymptomatic or mild ventricular arrhythmias and had recently had a heart attack. The study showed that the drugs actually increased the likelihood of death due to arrhythmias . Because it showed that some of the medicines were not safe, the study ended early and changed the way arrhythmias are treated today.
• Surgery versus medicine: The NHLBI-supported Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial compared catheter ablation, which is a common procedure to treat atrial fibrillation , a type of arrhythmia, with medicine. More than 2,200 patients participated in the study around the world. The researchers found that catheter ablation was no better than medicines at treating atrial fibrillation. However, patients who got catheter ablation experienced fewer symptoms and had a better quality of life than those who got the medicine alone. Read more about the results of this study: Surgery no better than medication at preventing serious complications of atrial fibrillation .
• Impact of genetic factors: In 2002, NHLBI-supported researchers identified a gene variant that is associated with arrhythmia in African Americans. The study found that when the variant is combined with other risk factors such as taking certain medicines or having low blood potassium or heart disease, the risk of life-threatening arrhythmias is increased.
• Risk factors for arrhythmias: The NHLBI supports several long-term studies to better understand the risk factors for heart disease. The Atherosclerosis Risk in Communities (ARIC) study found that having an arrhythmia, specifically premature beats in the heart’s ventricles, may increase a person’s risk of stroke. ARIC also helped define factors that increase the risk of arrhythmias. Another ARIC study looked at racial differences in atrial fibrillation . The study found that African Americans are less likely than whites to have atrial fibrillation but more likely to have poor outcomes, including stroke, heart failure, and death. Data from ARIC and the Framingham Heart Study have also been used to develop models for predicting a patient’s risk of atrial fibrillation.

These studies and others that the NHLBI funds continue to explore how lifestyle habits, other heart and blood vessel diseases, stress, and genes are linked to arrhythmias and how these risk factors affect different populations. Data from these studies are available through the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) and the Trans-Omics for Precision Medicine (TOPMed) Program .

Current research funded by the NHLBI

Our Division of Cardiovascular Sciences and its Adult and Pediatric Cardiac Research Program and Heart Failure and Arrhythmias Branch oversee much of the research that NHLBI supports on arrhythmias.

Current research on developing new methods to diagnose and monitor arrhythmias

Technology advances: Through a Small Business Innovation Research grant, the NHLBI supported the development of the RHYTHMIA HDx™ Mapping System. This innovative technology accurately measures the heart’s electrical activity and provides 3-dimensional maps detailing how well the heart is working. This can help doctors more accurately diagnose arrhythmias to select the right treatment option for each patient. 

Find  funding opportunities  and  program contacts  for arrhythmias research.

Find more NHLBI-funded studies on diagnosing and monitoring  arrhythmias  at NIH RePORTER.

Current research on causes of arrhythmias 

NHLBI-supported research has helped reveal how lifestyle habits, certain medicines, our genes, and stress can lead to arrhythmias. We continue to fund studies to further explore the causes and risk factors of arrhythmias. 

• Computer-based screening: Several medicines can raise the risk of arrhythmias. We fund research to  develop computer programs to screen new medicines  to identify those that are likely to cause or worsen arrhythmias. 
• Obesity's impact on the heart: We fund research into  how obesity and fat deposits around the heart  can raise the risk of atrial fibrillation. 
• Genetic studies: We support large-scale genomic studies to find genes that are linked to arrhythmia , including studies conducted through an international atrial fibrillation consortium, AFGen . Other studies are exploring whether  certain genes raise the risk of arrhythmias after heart surgery  and identifying which changes to the genes that control our heart rhythm are harmless and which  changes cause specific types of arrhythmias . 

Find more NHLBI-funded studies on the  causes of arrhythmias  at NIH RePORTER. 

Current research on diagnosing and monitoring arrhythmias 

The NHLBI supports research to improve imaging technology to diagnose and monitor arrhythmias. 

• Magnetic-resonance imaging (MRI) technology: We fund research to develop and test new MRI technology to monitor scar tissue formation in specific areas of the heart after treatment for arrhythmias. 
• Better MRI cardiac images: We support research to improve the quality of cardiac MRI images in people who use an implantable electronic device such as a pacemaker to prevent or treat arrhythmia. 

Learn more about how the NHLBI is supporting the development of new technologies to improve heart health: Highlights in Heart Health . 

Find more NHLBI-funded studies on  diagnosing arrhythmias  at NIH RePORTER. 

Research on treatments for arrhythmia 

The NHLBI supports research to develop innovative treatments for arrhythmias to help limit complications and improve quality of life. In a study of ventricular tachycardia (a fast rhythm), researchers developed a noninvasive catheter-free method for mapping and treating the area of the heart where the abnormal rhythm originates. The procedure combines cardiac imaging and electrocardiography (EKG) with stereotactic body radiation therapy — originally developed to deliver precise, high-dose radiation to tumors.

Current research includes:

• New medicines: We fund basic science and pharmacology studies to develop and test the safety of new types of medicines to treat arrhythmias . 
• Genetic therapies: We support studies to develop  genetic therapies  to correct gene mutations that cause arrhythmias . 
• Effectiveness and safety of current treatments: A type of arrhythmia called atrial fibrillation is a common complication of long-term kidney disease. We support research to explore whether the medicines and procedures commonly used to treat atrial fibrillation are safe and effective in people who have kidney disease. 
• Sudden cardiac arrest: Many people who have arrhythmias have no symptoms and may not know that they have this condition until they have  cardiac arrest . The NHLBI funds research to  improve methods to restart the heart during cardiac arrest  and to prevent repeated events of cardiac arrest. 

Find more NHLBI-funded studies on  treatments for arrhythmias  at NIH RePORTER.

Arrhythmia research labs at the NHLBI

Our Division of Intramural Research (DIR) and its Cardiovascular Branch conduct research on diseases that affect the heart and blood vessels. Specific projects aim to answer clinically relevant questions in diagnostics, therapeutics, and interventions. For example, NHLBI researchers developed an improved, more precise method of catheter ablation to treat problems causing arrhythmia. The technique, called interventional cardiovascular MR (iCMR), uses magnetic resonance imaging (MRI) to guide the placement of the catheter in the heart.

Other DIR groups, such as the Systems Biology Center , perform research on heart and vascular diseases.

Related arrhythmias programs

Supporting heart health in women

The NHLBI created  The Heart Truth®  in 2002 to raise awareness about heart disease as the leading cause of death in women. The Heart Truth is focused on making sure that women know about their risk for heart disease and know that healthy lifestyle changes can lower this risk. The program provides free science-based educational materials and information about heart-healthy living  and coordinates activities for  American Heart Month .

Learn more about the NHLBI’s work to improve heart health in women: Advancing Women’s Heart Health .

Studying innovations to improve heart and vascular disease outcomes

The Cardiothoracic Surgical Trials Network (CTSN) is an international network that studies heart valve disease, arrhythmias, heart failure, coronary heart disease, and the complications of surgery. CTSN researchers have worked to improve outcomes for people who have atrial fibrillation and need heart valve surgery. Researchers have also compared treatments that helped control heart rate and treatments that helped control heart rhythm as a first treatment option after surgery.

Find Arrhythmias Clinical Trials .

Explore more NHLBI research on arrhythmias

The sections above provide you with the highlights of NHLBI-supported research on arrhythmias . You can explore the full list of NHLBI-funded studies on the NIH RePORTER .

To find more studies:

• Type your search words into the  Quick Search  box and press enter. 
• Check  Active Projects  if you want current research.
• Select the  Agencies  arrow, then the  NIH  arrow, then check  NHLBI .

If you want to sort the projects by budget size — from the biggest to the smallest — click on the  FY Total Cost by IC  column heading.

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Arrhythmia and its risk factors post myocardial infarction

A prospective study.

Sharma, Rajinder; Chowdhary, Ishfaq; Sharma, Ankita

Department of Medicine, Government Medical College, Jammu, India

To whom correspondence may be addressed. E-mail: [email protected]

Received September 10, 2021

Received in revised form December 27, 2021

Accepted January 10, 2022

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Objectives: 

To determine the occurrence of arrhythmia and its associated risk factors in the first week after acute myocardial infarction (MI).

Methods: 

A total of 100 patients with acute MI were recruited, who were followed up for one week to determine the occurrence of arrhythmia and its association with electrolyte disturbances, left ventricular ejection fraction (LVEF), and demographic factors. Univariate and multivariate logistic regression was used to identify significant risk factors of arrhythmia.

Results: 

Among 100 cases, arrhythmia was seen in 27 patients. Sinus tachycardia was the commonest, followed by ventricular premature beats and sinus bradycardia. Ejection fraction, serum calcium and magnesium were significantly different between non-arrhythmia and arrhythmia patients ( P <0.05). Multivariate logistic regression analysis showed that ejection fraction was an independent significant risk factor of arrhythmia. Patients with ejection fraction >40% had a significantly lower risk of arrhythmia with an adjusted odds ratio of 0.22 (95% CI : 0.08 to 0.64).

Conclusions: 

Arrhythmia is common in the first week after myocardial infarction. The type of arrhythmia and the type of block may depend on the heart muscles involved during myocardial infarction. Ejection fraction is a risk factor that may affect the occurrence of arrhythmia.

1. Introduction

Cardiovascular diseases (CVDs) (including mainly ischemic heart disease (IHD) as well as stroke) are considered to be one of the main causes of worldwide mortality as well as morbidity, and primary contributors in disability[ 1 ]. World Health Organization and Global Burden of Disease study report around 18.6 million deaths from CVD in the past year[ 2 ].

Acute myocardial infarction (AMI) and the complications associated with it are considered to be the most life-threatening in atherosclerotic coronary artery diseases (CAD). Most of the mortality in AMI is caused by arrhythmia that include atrioventricular block, bradyarrhythmias, supraventricular tachyarrhythmias, and ventricular arrhythmias[ 3 4 ]. Along with arrhythmia present in the acute phase of MI, the risk related to arrhythmia is increased more due to the reopening of an infarct-related artery; this can lead to serious arrhythmia, eventually increasing the risk of mortality[ 4 ]. This has been ascribed to the disturbances in serum electrolytes that are common in the initial 24 h after AMI. Several inorganic salts (particularly alkaline elements) consisting of sodium as well as potassium are implicated among experiments for disbalance in the cardiac rhythm[ 5 ].

Though the initial 48-72 h are monitored with caution, less attention is paid to the convalescent period of AMI, whereas patients still are at risk of severe cardiac arrhythmia as well as sudden death[ 6 ].

In patients of Indian origin, there is sparse data related to the profile and timing of arrhythmia within 1-7 d of acute MI as well as the factors that increased the probability of such events[ 7 ].

Thus the present study was conducted to determine the occurrence of arrhythmia and their associated risk factors in the first week after AMI.

2. Patients and methods

2.1. study design.

A prospective study was conducted in the Department of Medicine of a tertiary care hospital in Jammu over 12 months from November 2018 till October 2019.

2.2. Inclusion and exclusion criteria

All diagnosed cases of AMI were included in the study admitted during the study period. Patients with less than 18 years of age, presence of congenital heart disease, or valvular heart disease were excluded from the study ( Figure 1 ).

2.3. Sample sizes

Sample size calculation based on the study of Shah et al .[ 8 ] who observed that the incidence of arrhythmia was 41%. Taking this value as reference, the minimum required sample size with a 10% margin of error and 5% level of significance is 93 patients. To reduce the margin of error, the total sample size taken is 100.

2.4. Ethical consideration

Written informed consent was obtained from all the patients before enrollment and institutional ethical clearance was obtained before beginning the study (IEC/GMC/2019/813, Dated 16.12.2019).

2.5. Diagnosis

The diagnosis of AMI was based on typical signs and symptoms, chest pain, and ECG findings suggestive of ST-segment elevation myocardial infarction (STEMI) for non-STEMI and elevated cardiac biomarkers like creatine phosphokinase and troponin T.

2.6. Data collection

All patients underwent routine blood investigation, 12 lead electrocardiogram, 2D echocardiography, serum electrolytes, cardiac biomarkers, and cardiac monitoring. During the follow-up period of 7 d after AMI, the occurrence of arrhythmia and its types were recorded as an outcome measure. Secondarily, we determined the association of various demographic and clinical parameters with the occurrence of arrhythmia.

2.7. Statistical analysis

The data entry was done in the Microsoft EXCEL spreadsheet and the final analysis was done with the use of Statistical Package for Social Sciences (SPSS) software (IBM manufacturer, Chicago, USA, ver 21.0.). Kolmogorov-Smirnov test was used to determine the normality of the data. The categorical variables was presented in the form of numbers and percentages (%). The quantitative data with normal distribution were presented as the means ± SD. The age data were quantitative and were analyzed using an independent t -test. The comparison of the variables which were qualitative such as gender, ejection fraction, serum sodium, and serum calcium was analyzed using the Chi-square test. If any cell had an expected value of less than 5 then Fisher's exact test was used for the association of serum potassium and magnesium with arrhythmia. Multivariate logistic regression was used to find out significant risk factors of arrhythmia. The significance level of this test was α=0.05.

The mean age of the patients was (56.60±12.72) years (range: 25-89 years) with the gender distribution of 68% males and 32% females. The comorbidities seen among the study population were hypertension and diabetes. There were 40% smokers who smoked around 8-10 cigarettes per day for a median duration of 5 years, while there were 50% alcoholics who consumed around 90 mL of alcohol daily for a median duration of 2 years. The commonest complaint was chest pain as seen in 94% of cases followed by dyspnea, sweating, vomiting, palpitations, and epigastric pain [ Table 1 ].

Of all 100 cases, 82% had STEMI and 18% had non-STEMI (NSTEMI). It was observed that 34% had extensive anterior wall infarction, 21% had inferior wall infarction, 12% had anteroseptal, 19% had inferior wall with right ventricular extension and 6% had anterolateral MI.

Among 100 cases, the incidence of arrhythmia was 73%, and among the 73 cases the most common arrhythmia was sinus tachycardia detected in 30 cases (41.1%), followed by ventricular premature beats in 17 cases (23.2%), sinus bradycardia in 16 cases (21.9%), ventricular tachycardia in 6 cases (5.8%) and atrial fibrillation in 6 cases (8.3%). However, ventricular fibrillation and atrial flutter was not seen in any of the patients. Of all cases, the incidence of the block was seen in 24 cases out of which 8 had left bundle branch block (33.3%), 6 had right bundle branch block (25.0%), 4 had 2nd-degree heart block (16.7%) and 6 had complete heart block (25.0%).

Most of the arrhythmias were seen between 1-12 h following acute infarction, among which 35.4% of the cases showed arrhythmia immediately within 1 h, 45.6% of cases between 1-12 h, 11.6% between 12 h and 48 h, and 7.4% between 3rd to 5th day. Cardiac failure (ejection fraction<40%) was seen in 51% cases. Ejection fraction, serum calcium, and magnesium were significantly different between non-arrhythmia and arrhythmia patients ( P <0.05) [ Table 2 ].

Multivariate logistic regression showed that ejection fraction was an independent significant risk factor of arrhythmia. Patients with ejection fraction >40% had a significantly lower risk of arrhythmia with an adjusted odds ratio of 0.22 (95% CI : 0.08 to 0.64) [ Table 3 ].

4. Discussion

Follow-up of the patients with MI seems necessary because of the occurring of arrhythmia which carry a high morbidity and mortality. In MI non-availability of oxygen causes heart muscles to damage irreversibly. The diastolic and systolic function gets impaired in a MI patient, which increases the susceptibility to arrhythmia. MI results when the heart muscle gets damaged due to a stoppage of blood flow, which increases myocardial metabolic demand, decreases oxygen delivery, decreases delivery of nutrients to the heart's muscles (via coronary circulation)[ 9 ].

In our study, there were 27% cases of arrhythmia among which sinus tachycardia was the commonest. This mainly occurs because of ionic alteration and electrolyte disturbances as they disturb the electrical activity of the sinoatrial node causing a block in the conduction, the processes which account for the occurrence of arrhythmia. It must be remembered that arrhythmia is not only a sequel of MI but they are also seen during the process of MI[ 8 ].

The mechanisms responsible for cardiac arrhythmia may be divided into disorders of impulse formation, disorders of impulse conduction, or a combination of both[ 10 ]. The autonomic nervous system controls the activity of the pacemaker. Systemic factors modulate the action of the pacemaker, which includes endogenous or pharmacological substances and metabolic abnormalities. The parasympathetic system releases acetylcholine, which increases the potassium channel conductivity. It also decreases the activity of myocyte L-type voltage-sensitive calcium channel current, which impacts the rate further down[ 10 ].

Failure of conduction of transmitting impulse leads to conduction delay and block. Conduction velocity of an impulse and conduction success is dependent on many factors that include both active and passive membrane properties. These factors are the impulse's stimulating efficacy and the tissue excitability, in which the impulse is conducted[ 11 ].

The coupling of the gap junction is a critical factor in determining the safety and velocity of impulse transmission. At high rates, refractoriness is not recovered completely, which leads to impulse blockage. If an impulse reaches a tissue that is still under refractory period, the impulse will not be either conducted or conducted with deviation. This mechanism explains many phenomena like Ashman's phenomenon during atrial fibrillation, block or functional bundle branch conduction of a premature beat, and acceleration-dependent aberration[ 10 ].

The occurrence of arrhythmia depends on the wall of the heart that is predominantly affected by MI. Seen in the present study that anterior and the inferior wall MI were the commonest, and the type of arrhythmia commonly seen were sinus tachycardia, ventricular premature beats, and sinus bradycardia with various types of conduction blocks. The findings were in line with various other studies where anterior and inferior wall MI was the commonest, and sinus tachycardia with ventricular premature beats was significantly associated with it[ 8 ].

In addition, the left ventricular ejection fraction after MI becomes an important predictor of arrhythmia. We determined that if the left ventricular ejection fraction was more than 40% there was significantly less chance of the occurrence of arrhythmia. This indirectly shows that the heart muscles are working in good conditions and the electrical conductivity has been maintained. Besides one may also use global longitudinal strain as a marker to assess the recovery of cardiac muscles while predicting the occurrence of arrhythmia however future studies are recommended to validate that same.

Besides, electrolyte levels also have a significant impact on the prognosis of patients with myocardial infarction. AMI has been reported to be monitored using changes in electrolyte levels. There are various types of electrolytes present in the body, each with a distinct and significant function; however, majority are involved in the maintenance of the fluid balance between the intracellular (within the cell) and extracellular (outside the cell) environments[ 9 ].

It is important to maintain balance as it is helpful in the maintenance of hydration, nerve impulses, normal functioning of muscles, and maintaining pH level. The main electrolytes present in the body include sodium, potassium, magnesium, calcium, and chloride. The significant factors for the determination of electrophysiological properties related to the myocardial membrane are serum sodium, potassium, and chloride[ 9 ].

Among the various electrolyte disturbances, hypocalcemia and hypomagnesemia showed a significantly higher risk in association with arrhythmia. Calcium maintains depolarization and is involved in myocardial contractility while magnesium stabilizes the cell membrane and acts in concert with potassium and is a calcium antagonist. It dilates coronary arteries, peripheral systemic arteries and reduces afterload. Few studies have been done till now and less information is available in the literature about the prognostic value of serum electrolytes in ischemic heart diseases. Patil et al .[ 12 ] reported that in patients with AMI, maximum electrolyte imbalance was present in calcium. In about 50% of cases, hypocalcemia was noted and one of the studies[ 13 ] showed a correlation between hypomagnesemia and ventricular arrhythmia.

Though not seen in our study, sodium and potassium (two of the complex electrolytes present in the body) have also been seen to be associated with arrhythmia[ 14 15 16 ]. Wali et al .[ 16 ] in a case-control study ( n =50), including patients with AMI, found a significant reduction in levels of sodium and potassium among cases. Similar findings were reported by Hariprasad et al .[ 17 ] as it was found that AMI patients had reduced levels of sodium and potassium. Some studies partly corroborated with the study in finding no association of sodium or potassium levels with the occurrence of arrhythmia[ 17 ].

A study by Verma et al .[ 5 ], including 75 patients with AMI with or without arrhythmia, found that concentration of serum sodium was unaffected among patients having AMI with or without arrhythmia while the concentration of serum potassium was significantly reduced among patients with AMI with arrhythmia.

Ventricular arrhythmia as well as consequent sudden cardiac death because of the AMI are the most frequent causes of death among humans. Lethal ventricular arrhythmia, such as ventricular fibrillation (VF), before hospitalization is reported to be present in >10% of all the cases of AMI with the survival among such patients being poor[ 18 ].

Therefore, recognizing the risk factors, as well as mechanisms related to VF after AMI is significant, which can aid in the implementation of novel risk stratification models and therapeutic methods for decreasing mortality among individuals having high CV risk. Usually, evaluation of spontaneous VF after AMI is difficult because it generally takes place unexpectedly among the low-risk subgroup[ 18 ]. However, our results show disturbed electrolyte disturbances in the initial 7 d following AMI which may provoke arrhythmia and increase morbidity and mortality.

Though there was no mortality observed in the present study but it still amounts to a limitation. The treatment protocol was not recorded in the present study. Lastly, the study population sample size was small.

It can be concluded that arrhythmia is a common occurrence in the initial follow-up week after myocardial infarction. The type of arrhythmia and the type of block may depend on the heart muscles involved during myocardial infarction. Ejection fraction is a significant risk factor that may affect the occurrence of arrhythmia.

Conflict of interest statement

The authors report no conflict of interest.

Authors’ contributions

R.S.: Concept, design, literature search, data analysis, manuscript preparation; I.C.: Design, Data acquisition, manuscript review; A.S.: Design, Data acquisition, manuscript review.

Arrhythmia; Myocardial infarction; Left ventricular ejection fraction

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Article Contents

Introduction, conclusions, supplementary material.

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Risk of arrhythmias after myocardial infarction in patients with left ventricular systolic dysfunction according to mode of revascularization: a Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) substudy

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Anna F Thomsen, Peter Karl Jacobsen, Lars Køber, Rikke Moerch Joergensen, Heikki V Huikuri, Poul Erik Bloch Thomsen, Uffe G Jacobsen, Christian Jøns, Risk of arrhythmias after myocardial infarction in patients with left ventricular systolic dysfunction according to mode of revascularization: a Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) substudy, EP Europace , Volume 23, Issue 4, April 2021, Pages 616–623, https://doi.org/10.1093/europace/euaa273

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The Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) study was an observational trial including 312 patients with acute myocardial infarction (MI) and left ventricular ejection fraction (LVEF) <40%. Primary percutaneous intervention (pPCI) was introduced 2 years after start of the enrolment, dividing the population into two groups: pre- and post-pPCI. This substudy sought to describe the influence of the mode of revascularization on long-term risk of new-onset atrial fibrillation (AF), bradyarrhythmia, and ventricular tachycardia and the subsequent risk of relevant major cardiovascular events (MACE).

The study included the 268 patients without a history of AF. All patients received an implantable cardiac monitor (ICM) and were followed for 2 years. The choice of revascularization was made by the treating team independently of the trial and retrospectively divided into pPCI, subacute PCI, primary thrombolysis, or no revascularization. Endpoints were new-onset arrhythmia and MACE.

A total of 77 patients received no revascularization, whereas 49 received thrombolysis only and 142 received any PCI. The adjusted hazard ratio (HR) for developing any arrhythmia and the subsequently risk of MACE were increased in non-revascularized or thrombolysed patients compared with PCI-patients (any arrhythmia, non-revascularization: HR = 1.7, P  = 0.01 and thrombolysis: HR = 1.6, P  = 0.05; MACE, non-revascularization: HR = 3.1, P  = 0.05 and thrombolysis: HR = 3.1, P  = 0.08). All HRs were adjusted for significant baseline and clinically considered covariates and stratified for calendar year.

This study is the first to demonstrate that the long-term risk of arrhythmia documented by an ICM and the subsequent risk of MACE were increased in non-revascularized or thrombolysed patients compared with PCI-patients in a post-MI population with LVEF <40%.

The long-term risk of any arrhythmia documented by an implantable cardiac monitor was increased in patients non-revascularized or thrombolysed compared with percutaneous intervention (PCI)-treated patients.

Patients non-revascularized or thrombolysed had a three-fold increased risk of major cardiovascular events (MACE) subsequent to new-onset arrhythmia compared with patients not developing any arrhythmia or PCI-treated patients with new-onset arrhythmia.

The risk of MACE was equal in PCI-treated patients developing any new-onset arrhythmia compared with patients with or without PCI treatment not developing any arrhythmia.

Acute and evolving myocardial ischaemia is well described to be highly arrhythmogenic due to severe metabolic and electrophysiological changes, hereby closely related to deterioration in heart failure and sudden cardiac death. 1 , 2 The introduction of percutaneous intervention (PCI) as first choice treatment has reduced the risk of re-infarction, stroke, and death in MI patients compared with traditional thrombolytic therapy. 3 Recent results have implied that the development of acute malignant bradycardia, such as high-degree atrioventricular block (AVB), has decreased with PCI as first choice treatment, 4 but the risk of arrhythmias has never been investigated in long-term studies.

The Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) study was the first to investigate the development of new onset arrhythmias in patients with left ventricular systolic dysfunction after an acute myocardial infarction (MI) using an implantable cardiac monitor (ICM) for continuous cardiac monitoring for 2 years. 5 The results showed that 80–90% of serious arrhythmias were asymptomatic and >70% of all major endpoints were preceded by an arrhythmia. 6–11

During the study inclusion from 2000 to 2005, recommendations for percutaneous coronary interventions changed, as primary percutaneous coronary intervention (pPCI) was introduced about midway (2002) on the enroling centres. Therefore, the study population contains a relatively unbiased mixture of patients that were initially primarily treated with thrombolysis while later mainly received primary or subacute PCI.

The purpose of this study was to examine the influence of the mode of revascularization on the long-term risk of new onset atrial fibrillation (AF), ventricular tachyarrhythmias and bradyarrhythmias and the associated risk for relevant major cardiovascular events including heart failure, new (MI), stroke, and cardiac death using an ICM.

This study was performed as pre-specified substudy on a subgroup of the CARISMA study population described in detail elsewhere. 5 , 12 In summary, 312 patients were included in 10 European centres within the first 3 weeks after experiencing an MI. A total of 297 had an ICM. Of these, 26 had AF before enrolment (permanent AF n  = 10 and paroxysmal AF, n  = 16) and 3 had known bradycardia and received a permanent cardiac pacemaker. After exclusion, a total of 268 patients were included in the study. Importantly patients were excluded from the CARISMA study if the attending physician treating the patient or the patient refused participation in the study ( n  = 380), if the patient suffered from other serious illness ( n  = 312), if the patient was eligible for CABG ( n  = 184) or died ( n  = 89) before the implantation of the ICM and/or the risk stratification tests.

Myocardial infarction and revascularization

Myocardial infarction was defined as a significant rise in troponins as defined by the including centre at the time of enrolment accompanied by either (i) classical chest pain and/or (ii) ECG changes compatible with myocardial ischaemia. Choice of revascularization was made by the treating team independently of the trial and was retrospectively divided into pPCI, subacute PCI (24 h to 2 weeks after MI), primary thrombolysis ± subacute PCI or no revascularization. Recommendations and guidelines for percutaneous coronary interventions changed during the study period with the introduction of pPCI about midway (2002) in all the enroling centres.

The implantable cardiac monitor and diagnosis of arrhythmias

The ICM used in the study was the Reveal Plus ® (Medtronic Inc.). The ICM was implanted subcutaneously under local anaesthesia in the left parasternal area 5–21 days after an MI. The device was programmed to automatically store tachyarrhythmias at heart rates ≥125 b.p.m. lasting at least 16 consecutive beats, bradyarrhythmias at heart rates ≤30 b.p.m. lasting at least 4 beats or asystolic events lasting >4.5 s. According to this, arrhythmias were defined as follows:

Atrial fibrillation: irregular rhythm with no visible p waves and the presence of a fibrillatory line lasting ≥8 s.

Ventricular tachycardia (VT): non-sustained VT (NSVT) >125 bmp lasting >16 consecutive beats, sustained VT (SVT) lasting >30 s and ventricular fibrillation (VF).

Bradyarrhythmia: 2nd degree type II or 3rd degree AVB and sinus bradycardia (SB) ≤30 b.p.m. lasting >8 s, sinus arrest (SA) lasting >4.5 s.

The patients were followed up at 6 weeks, 3 months, and every 3 months hereafter until 2 years. The memory of the loop recorder was interrogated, and the sensitivity of arrhythmia detection was adjusted individually according to the number of false events at each visit. Every recorded event was initially classified locally by the investigator and after inclusion adjudicated by a blinded member of the steering committee. The ICM detected 70% of all tachyarrhythmias in the CARISMA study. 13

Major cardiovascular event (MACE) was defined as combined endpoint of re-infarction, stroke, hospitalization for heart failure, and cardiac death. Hospitalization for re-infarction, stroke, and heart failure were determined locally by the responsible physician. Mode of death was adjudicated by a central five-member Endpoint committee using a modified Cardiac Arrhythmia Suppression Trial (CAST) classification.

The CARISMA study complied with the Declaration of Helsinki, and the research protocol was approved by the locally appointed ethics committee. Informed consent was obtained from each patient.

Demographic and clinical baseline characteristics were tested for normality using the Shapiro–Wilk’s test and Student’s t -test, χ 2 test, and Wilcoxon test were used where appropriate. Time to first arrhythmic or major cardiovascular event was estimated using the cumulative incidence function (CIF). Graphic presentation of the cumulative probability was done using the CIF curve for univariate baseline covariates. All ICM-documented arrhythmias and major cardiovascular events were treated as time-dependent covariates with the index MI as the time of origin. Univariate and multivariate hazard ratios (HRs) were obtained from cox proportional hazard regression. Significant univariate risk factors for any new-onset arrhythmia were congestive heart failure (CHF), QRS > 120, and New York Heart Association (NYHA) II–III and for MACE: earlier MI, CABG, and CHF. Significant univariate HRs were added to the multivariate Cox-model along with significant baseline variables: age, earlier MI and CABG, NYHA II–III, ACE and anti-platelet treatment, Q-wave infarction, anterior located infarction, and left bundle branch block (LBBB) and clinically considered significant variables: gender, diabetes, and left ventricular ejection fraction (LVEF) at enrolment. None of the univariate risk factors was significant in multivariate analysis. In all cox proportional hazard regression analyses, we did stratification by calendar year (before and after 2002, where pPCI was introduced) to adjust for time of enrolment. If the multivariate Cox models could not accommodate all significant covariates, we did best subset selection using the branch-and-bound algorithm of Furnival and Wilson. We limited the maximum number of descriptive variables to 1 per 5 endpoint events to secure model stability. All analyses were performed with SAS version 9.4 (SAS Institute, Inc., Cary, NC, USA). Two-sided P values <0.05 were considered significant.

A total of 77 patients received no revascularization, whereas 49 were treated with thrombolysis only and 142 at some point before ICM implantation had PCI (pPCI: n  = 63 and subacute PCI: n  = 79) ( Figure  1 ). The baseline characteristics of the study population are shown in Table  1 by groups of revascularization. Patients treated with thrombolysis only were slightly older, but generally the age in the population was relatively narrowly distributed around a mean age of ∼64. The medical treatment was balanced in the three groups, although patients not revascularized were less often treated with angiotensin-converting enzyme inhibitors and thrombolysed patients were less often in anti-platelet therapy.

Mode of revascularization in the CARISMA substudy. CARISMA, Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction.

Baseline characteristics at enrolment

ACE-I, ACE inhibitors; ATII, angiotensin II receptor antagonist; BBB, bundle branch block; CABG, coronary artery bypass graft; COPD, chronic obstructive pulmonary disease; LVEF, left ventricular ejection fraction; LVESD, left ventricular end systolic diameter; LVEDD, left ventricular end diastolic diameter; MI, myocardial infarction.

The distribution of multivessel disease, level of cardiac biomarkers, and LVEF at enrolment were equal in all three groups. In multivessel disease, anterior infarct accounted for 49% of the MIs. Patients not revascularized more often had a history of earlier CABG, CHF, LBBB, wide QRS >120, and together with thrombolysed patients more often reported heart failure symptoms corresponding to NYHA classes II–III. Significantly 60% of the non-revascularized patients had a history of an earlier MI. We found earlier MI to be associated with a significant higher frequency of multivessel disease (52%), earlier CABG (41%), NYHA classes II–III (85%), lateral infarction (30%), and less often q-wave infarction (44%) in comparison with patients with no history of an earlier MI.

Risk of new-onset arrhythmias

The multivariate HRs with 95% confidence limits for time to first arrhythmic event with patients treated with PCI as reference group are shown in Table  2 . No revascularization was significantly associated with increased risk of any arrhythmic event compared with patients treated with PCI (HR= 1.7, P  = 0.01). When investigating the different types of arrhythmias, non-revascularized patients had an over three-fold increased risk of VT including SVT and VF (HR = 3.4, P  = 0.03), whereas patients treated with thrombolysis only had an almost three-fold increased risk of bradyarrhythmia (HR = 2.7, P  = 0.02).

Results from Cox proportional hazards regression

Multivariate HR for time to first arrhythmic event with patients treated with PCI as reference group. Adjusted for significant univariate risk factors, significant baseline variables, and covariates which were clinically relevant b and stratified for calendar year.

CABG, coronary artery bypass graft; CHF, congestive heart failure; HR, hazard ratio; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association.

Ventricular tachycardia including sustained ventricular tachycardia and ventricular fibrillation.

Age, gender, earlier MI and CABG, CHF, diabetes, NYHA II–III, ACE and anti-platelet treatment, Q-wave infarction, QRS > 120, LBBB, LVEF at enrolment, and anterior located infarction.

The CIF curves in Figure  2 show the absolute risk for all arrhythmias ( Figure  2 A ), AF ( Figure  2 B ), bradyarrhythmia ( Figure  2 C ), and VT including SVT and VF ( Figure  2 D ) divided into mode of revascularization. The graphs demonstrate a strong association between new-onset arrhythmia and the mode of revascularization. The most frequent arrhythmia was AF (no revascularization: n  = 33, thrombolysis only: n  = 14, and PCI: n  = 37), followed by bradyarrhythmia (no revascularization: n  = 15, thrombolysis only: n  = 12, and PCI: n  = 14), and lastly VT including SVT and VF (no revascularization: n  = 12, thrombolysis only: n  = 3, and PCI: n  = 6). The number of events were AF (no revascularization: n  = 187, thrombolysis only: n  = 105, and PCI: n  = 242), bradyarrhythmia (no revascularization: n  = 85, thrombolysis only: n  = 77, and PCI: n  = 54), and VT including SVT and VF (no revascularization: n  = 16, thrombolysis only: n  = 8, and PCI: n  = 15). When considering the subgroups of each arrhythmia (VT: NSVT, VT, and VF and bradyarrhythmia: AVB, SA, and SB), the most frequent type of VT was NSVT with a cumulative risk of 21% in patients not revascularized, and the most frequent type of bradyarrhythmia was AVB with a cumulative risk of 13% in patients treated with thrombolysis only. However, the number of arrhythmic events in all subgroups was very low and conclusions must be taken with caution.

Cumulative incidence function curves depicting the probability of an arrhythmic event over time divided into mode of revascularization in post-MI patients treated with any PCI, thrombolysis only, or no revascularization. ( A ) The probability of an overall arrhythmic event, ( B ) the probability of atrial fibrillation, ( C ) the probability of bradyarrhythmia, and ( D ) the probability of ventricular tachycardia including sustained ventricular tachycardia and ventricular fibrillation. *Adjusted hazard ratio. MI, myocardial infarction; PCI, percutaneous intervention.

We found no significant difference in the 2-year cumulative risk of any arrhythmia or subgroups of arrhythmia, when investigating primary PCI vs. subacute PCI only vs. both primary thrombolysis and subacute PCI.

Congestive heart failure, QRS >120 ms, and NYHA II–III were significant univariate risk factors for any new-onset arrhythmia but not in multivariate analysis.

Risk of major cardiovascular events

The multivariate HRs with 95% confidence limits for time to first re-AMI, stroke, hospitalization for heart failure, or cardiovascular death event subsequent to new-onset arrhythmia are shown in Table  3 . A CIF curve in Figure  3 depicts the probability of a MACE subsequent to any new-onset arrhythmia vs. no new-onset arrhythmia. Patients with new-onset arrhythmia had a subsequently 2-year cumulative risk of 30% and significant HR of 2.2 of MACE compared with patients with no new-onset any arrhythmia irrespective of type of revascularization (HR = 2.2, P  = 0.01) ( Table  3 ). Non-revascularization or thrombolysis only was strongly associated with an three-fold increased risk of MACE subsequent to any new-onset arrhythmia compared with patients not developing any arrhythmia (no revascularization: HR = 2.9, P  = 0.01 and thrombolysis only: HR = 3.7, P  = 0.01), whereas the risk of MACE subsequent to new-onset arrhythmia was equal in PCI patients compared with patients not developing any arrhythmia (HR = 1.1, P  = 0.81) ( Table  3 ). The risk of MACE subsequent to new-onset arrhythmia in patients not revascularized or thrombolysed only was close to unchanged with PCI patients developing any new-onset arrhythmia as reference group (no revascularization: HR = 3.1, P  = 0.05 and thrombolysis only: HR = 3.1, P  = 0.08) ( Table  3 ). When investigating the risk of MACE with matching patients not developing any arrhythmia as reference group, patients not revascularized and thrombolysed only had an over two-fold risk of MACE subsequent to new-onset arrhythmia (no revascularization: HR = 2.2, P  = 0.04 and thrombolysis only: HR = 2.7, P  = 0.03) compared with patients not revascularized or thrombolysed only with no new-onset arrhythmia, whereas PCI patients had an insignificant reduced risk of MACE subsequent to new-onset arrhythmia compared with PCI patients with no new-onset arrhythmia (HR = 0.6, P  = 0.40) ( Table  3 ). We found an insignificant independent association between mode of revascularization and MACE with PCI patients as reference group (non-revascularized patients: HR = 1.5, P  = 0.25 and thrombolysed patients: HR = 1.8, P  = 0.16).

Cumulative incidence function curve depicting the probability of a major cardiovascular event over time in post-MI patients developing any arrhythmia vs. no arrhythmia. *Adjusted hazard ratio. MI, myocardial infarction.

Results from Cox proportional hazards regression.

Multivariate HR for time to first re-AMI, stroke, hospitalization for heart failure, or cardiovascular death event subsequent to new-onset arrhythmia. Adjusted for significant univariate risk factors, significant baseline variables, and covariates which were clinically relevant a and stratified for calendar year.

CABG, coronary artery bypass graft; CHF, congestive heart failure; HR, hazard ratio; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; MACE, major cardiovascular events; MI, myocardial infarction; NYHA, New York Heart Association; PCI, percutaneous intervention.

Age, gender, earlier MI and CABG, CHF, diabetes, NYHA II–III, ACE and anti-platelet treatment, Q-wave infarction, LBBB, LVEF at enrolment, and anterior located infarction.

This study is a non-randomized prospective multicentre study holding unique and historical data from both the thrombolytic era and the introduction of primary PCI.

Our study revealed that non-revascularization was strongly associated with a long-term risk of any new-onset arrhythmia with an over three-fold increased risk of malignant VT compared with patients treated with any PCI ( Table  2 ). Patients treated with thrombolysis only had a borderline significant increased risk of new-onset arrhythmia with an over two-fold increased risk bradyarrhythmia compared with patients treated with any PCI ( Table  2 ).

There are limited data investigating the association between mode of revascularization and long-term risk of arrhythmias. Few studies have implied that the risk of brady and tachy arrhythmias have declined with PCI as first choice treatment. 4 , 14 , 15 A single retrospective study has demonstrated that outcomes as low thrombolysis in myocardial infarction flow and incomplete ST resolution after PCI were associated with significantly higher risk of late VT, 16 yet patients were only followed for 90 days by regular ECG. The study by Gang et al . 4 demonstrated that the incidence of AVB complicating STEMI has decreased with the implementation of pPCI, but the investigators did not include a control group and data was registry based, which may underestimate the AVB incidence. With our study we demonstrate that not only has PCI treatment improved the acute risk of new onset AF, ventricular tachyarrhythmias, and brady arrhythmias but also on long term.

In relation to MACE, patients not revascularized or thrombolysed only had a three-fold increased risk of MACE subsequent to new-onset arrhythmia compared with patients not developing any arrhythmia or PCI patients developing any arrhythmia ( Table  3 ). These supporting existing data on comparing traditional thrombolytic therapy with pPCI, 17 but no one has, as far as we know, described the long-term risk of MACE subsequent to new-onset arrhythmia in terms of mode of revascularization. Patients treated with any PCI had a reduced to equal risk of MACE subsequent to new-onset arrhythmia compared with both PCI and all patients not developing any arrhythmia.

The high incidence of new-onset malignant arrhythmias and the associated risk of MACE in non-revascularized patients most likely implies a common arrhythmic myocardial substrate due to ischaemia-driven myocardial adverse remodelling or electrophysiological instability due to underlying heart disease. We found that patients not revascularized were characterized by more progressive heart failure and extensive chronic ischaemia compared with patients treated with thrombolysis only or any PCI. Notably 60% of the non-revascularized patients had a history of an earlier MI associated with a high incidence of multivessel disease and NYHA classes II–III. Cardiac performance, coronary vessel status and the degree of revascularization may be relevant for the development and maintenance of severe arrhythmias following high risk of MACE as our study advocates. Still, these are only hypotheses and our data are limited due to the changes in guidelines and the missing information on the extent of revascularization. Current and emerging data suggest that completion with PCI is beneficial, 16 , 18 , 19 but future studies are warranted to consider the risk on long term arrhythmias in complete vs. incomplete revascularized myocardium as well as characterization of the arrhythmogenic substrate.

Study limitations

The findings of this study have to be seen in light of several limitations. First, the sample size was limited. Yet patients were monitored in much more details than any other study population. Secondly, we have no accurate data on the degree of revascularization in all patients. Thirdly, data could be biased due to over-time optimized medical treatment. Fourth, there was an unequal distribution of anterior located MI in the study population. Fifth, the use of beta-blocker could have had an impact on the number of arrhythmias detected by the ICM. Arrhythmias occurring outside the diagnostic window (30 b.p.m. ≤ heart rate ≤ 125 b.p.m.) were not systematically detected. Finally, the memory of the ICM contains 13 slots for automatic recording, hereafter the oldest recording is deleted when a new event is stored.

To our knowledge, this study is the first to reveal that the long-term risk of any arrhythmia documented by an implantable loop recorder and the associated risk of MACE were increased in patients not revascularized or thrombolysed compared with patients treated with PCI or not developing any arrhythmia in a population of survivors of an MI with reduced ventricular systolic function.

Supplementary material is available at Europace online upon request.

The authors received no financial support for this research. The main CARISMA study was supported by research grants from Medtronic Bakken Research Center, Maastricht, The Netherlands and Cambridge Heart Inc., MA, USA.

Conflict of interest: P.E.B.T. and H.V.H. have received research grants and speakers' fees from Medtronic Inc., St. Jude Medical, and Boston Scientific. The other authors have no financial conflicts of interest to disclose.

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• cardiac arrhythmia
• myocardial infarction
• thrombolytic therapy
• left ventricular systolic dysfunction
• revascularization
• cardiac monitors
• stratification

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A Prospective Study of Risk of Arrythmias in Patients with Myocardial Infarction in a Tertiary Care Center

Affiliation.

• 1 Mandya Institute of Medical Sciences, Mandya.
• PMID: 35443382

Acute Coronary Syndrome (ACS) is an emerging epidemic in India. Conduction blocks occur in about 15-20% of patients with acute MI, studies have shown that arrhythmias are important predictors of poor outcome in patients with ACS and are associated with higher in hospital mortality.In this study an attempt is made to know the association of arrhythmias in patients of acute MI. In acute MI sudden cardiac death can occurs due to arrhythmias.

Material: A Prospective clinical study consisting of 100 patients of acute coronary syndrome were taken to determine the occurrence of arrhythmia. All cases of ACS admitted in Mandya Institute of medical Sciences were taken in the study. All cases of ACS with age, less than 50yrs and more than 18yrs, admitted in MIMS, Mandya were studied.ECG at the time of admission, fourth hourly on day of admission, daily morning and as whenever needed, cardiac enzymes studies, and echocardiography were done. The patients were observed for conduction defects for 5 days after the admission or until they stay in the hospital whichever was earlier.

Inclusion criteria: Patients of acute myocardial infarction with age more than 18yrs and less than 50yrs, admitted to MIMS, Mandya.

Exclusion criteria: Previously known cases of conductions defects. -Patients on drugs, which may cause conductions defects, like Beta blockers, calcium channel blockers and Digoxin. -All cases with conduction defects due to other documented causes like structural abnormalities or electrolyte disturbances were excluded from the study. -Patient's with previous history of IHD.

Observation: A total of 100 patients are taken, which included 56 males and 44 females. In this present study out of 100 patients, 78 patients had arrhythmias, of that 40% were females and 38% were males. In this study 56% of arrhythmia occurred during the 1st hour, 24% of patients had arrhythmias during 12-24 hours, 19% of patients had arrhythmias after 24 hours. The most common type of arrhythmia was ventricular premature complexes(24.36%) followed by sinus tachycardia(16.67%) and atrial fibrillation(15.38%). The least common type of arrhythmia was 1st degree heart block (2.56%) in this study. Among the type of ACS, ST elevation MI was associated with increased risk of arrhythmia (71%), followed by Non ST-Elevation MI (23%) and Unstable angina (6%).

Conclusion: Arrhythmias associated with ACS are common, and may be related to more complicated comorbidity and more severe impairment of myocardium, and lead to a poorer prognosis. More attention should be paid to these patients to improve their treatment and prognosis.

© Journal of the Association of Physicians of India 2011.

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• [Types and risk factors of arrhythmia on young patients with acute coronary syndrome in Henan province]. Zhao J, He F, Hu DY, Ding RJ, Yu XJ, Gou JJ, Wang L, Zhang P, Li XB, Guo JH, Liu WL, Li CL, Li L, Gao CY, Zhao LS, Chu YJ, Huang ZW, Wei JH, Hua SH, Liu RY, Zhuang XF. Zhao J, et al. Zhonghua Xin Xue Guan Bing Za Zhi. 2013 Jul;41(7):572-6. Zhonghua Xin Xue Guan Bing Za Zhi. 2013. PMID: 24284184 Chinese.
• The incidence and prognostic significance of cardiac arrhythmias and conduction abnormalities in patients with acute coronary syndromes and renal dysfunction. Lisowska A, Tycińska A, Knapp M, Lisowski P, Musiał WJ. Lisowska A, et al. Kardiol Pol. 2011;69(12):1242-7. Kardiol Pol. 2011. PMID: 22219098
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Intra-procedural arrhythmia during cardiac catheterization: A systematic review of literature

Fatima a shaik.

Division of Cardiology, New York Presbyterian Queens Hospital, Flushing, NY 11355, United States

David J Slotwiner

Gregory m gustafson.

Division of Cardiology, New York Presbyterian Queens Hospital, Flushing, NY 11355, United States. gro.pyn@2009dux

Corresponding author: Xuming Dai, MD, PhD, FACC, FSCAI, Associate Professor, Division of Cardiology, New York Presbyterian Queens Hospital, 56-45 Main Street, Flushing, NY 11355, United States. gro.pyn@2009dux

Cardiac catheterization is among the most performed medical procedures in the modern era. There were sporadic reports indicating that cardiac arrhythmias are common during cardiac catheterization, and there are risks of developing serious and potentially life-threatening arrhythmias, such as sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and high-grade conduction disturbances such as complete heart block (CHB), requiring immediate interventions. However, there is lack of systematic overview of these conditions.

To systematically review existing literature and gain better understanding of the incidence of cardiac arrhythmias during cardiac catheterization, and their impact on outcomes, as well as potential approaches to minimize this risk.

We applied a combination of terms potentially used in reports describing various cardiac arrhythmias during common cardiac catheterization procedures to systematically search PubMed, EMBASE and Cochrane databases, as well as references of full-length articles.

During right heart catheterization (RHC), the incidence of atrial arrhythmias (premature atrial complexes, atrial fibrillation and flutter) was low (< 1%); these arrhythmias were usually transient and self-limited. RHC associated with the development of a new RBBB at a rate of 0.1%-0.3% in individuals with normal conduction system but up to 6.3% in individuals with pre-existing left bundle branch block. These patients may require temporary pacing due to transient CHB. Isolated premature ventricular complexes or non-sustained VT are common during RHC (up to 20% of cases). Sustained ventricular arrhythmias (VT and/or VF) requiring either withdrawal of catheter or cardioversion occurred infrequently (1%-1.3%). During left heart catheterizations (LHC), the incidence of ventricular arrhythmias has declined significantly over the last few decades, from 1.1% historically to 0.1% currently. The overall reported rate of VT/VF in diagnostic LHC and coronary angiography is 0.8%. The risk of VT/VF was higher during percutaneous coronary interventions for stable coronary artery disease (1.1%) and even higher for patients with acute myocardial infarctions (4.1%-4.3%). Intravenous adenosine and papaverine bolus for fractional flow reserve measurement, as well as intracoronary imaging using optical coherence tomography have been reported to induce VF. Although uncommon, LHC and coronary angiography were also reported to induce conduction disturbances including CHB.

Cardiac arrhythmias are common and potentially serious complications of cardiac catheterization procedures, and it demands constant vigilance and readiness to intervene during procedures.

Core tip: Cardiac catheterization is the most performed invasive procedure in the current healthcare system. Cardiac arrhythmias are common complications during the procedure. This review demonstrated a 0.14%-0.3% incidence of transient right bundle branch block during right heart catheterization in normal individuals, and a significantly higher risk of complete heart block (up to 6.3%) for individuals with pre-existing left bundle brunch block. Potentially life-threatening ventricular arrhythmias requiring either withdrawal of catheter or cardioversion could occur at the rates of 1%-1.3%. The incidence of significant arrhythmias during left heart catheterization has reduced by about 10 folds in the past half century, from 1.1% to 0.1%. Coronary interventions, as well as intracoronary imaging and measuring fractional flow reserve, carry increased risk of malignant arrhythmias, including up to 1% incidence of ventricular fibrillations. Constant telemetry monitoring is essential during cardiac catheterization.

INTRODUCTION

Cardiac catheterization procedures performed in the cardiac catheterization laboratory (CCL) often include right heart catheterization (RHC); left heart catheterization (LHC); and coronary angiography with or without intra-coronary interventions. Cardiac catheterization is one of the most commonly performed procedures in the modern healthcare system. In 2014, there were more than 1 million inpatient diagnostic cardiac catheterizations and 480000 coronary angiography performed in the United States alone[ 1 ]. Given the nature of the intracardiac or intracoronary instrumentation as part of the cardiac catheterization procedure, cardiac arrhythmias are common and often unavoidable. We systematically reviewed the published literature to provide a comprehensive overview of the incidence rates, impact on outcomes and potential approaches to minimize the risk of cardiac arrhythmias during cardiac catheterization procedures.

Catheter-induced cardiac arrhythmias during RHC may occur as soon as the catheter tip enters the right atrium, and while advancing through the right atrium, right ventricle, right ventricular outflow tract and the pulmonary artery. Observed arrhythmias include supraventricular arrhythmias [premature atrial contraction, supraventricular tachycardias (SVTs, including atrial fibrillation (AF), atrial flutter)], ventricular arrhythmias, premature ventricular contractions (PVCs), non-sustained or sustained ventricular tachycardia (NSVT or VT) and ventricular fibrillation (VF), as well as various conduction disturbances, such as right bundle branch block (RBBB) and complete heart block (CHB), especially in the setting of pre-existing left bundle branch block (LBBB)[ 2 , 3 ].

LHC studies typically include measuring the left ventricular pressures and performing left ventriculography with catheters crossing the aortic valve and positioned in the left ventricle, in addition to performing coronary artery angiography. Depending on the coronary angiographic findings, a percutaneous coronary intervention (PCI) may subsequently be performed. In addition, intravascular imaging such as intravascular ultrasound (IVUS) or optimal coherence tomography (OCT) may be used to examine coronary artery anatomy. Fractional flow reserve (FFR) may be applied to assess the hemodynamic significance of a coronary artery stenosis. This review summarizes arrhythmic complications of these procedures. Recently developed structural heart interventional procedures, i.e . transcatheter valvular therapies for valvular disease, often involve rapid pacing and have a potential to cause significant injury to the conduction system. Arrhythmias associated with structural heart interventions are not included in this review.

MATERIALS AND METHODS

We screened the titles and abstracts of studies against predefined terms, using PubMed, EMBASE and Cochrane databases (Table ​ (Table1). 1 ). The title and available abstracts of all returned articles were reviewed to identify relevant articles for a full-length review and follow-up of their references. We synthesized the following review according to the procedure and arrhythmia types. Meta-analysis was not performed due to the tremendous heterogeneity in inclusion criteria, equipment used in cardiac catheterization, and the arrhythmia definitions among reported studies.

Terms describing cardiac catheterization procedures and arrhythmias used in the combination for database search

Cardiac arrhythmic during RHC

RHC may be performed in the CCL, at the bedside of intensive care unit (ICU) or in the operating room. The majority of published studies on arrhythmias during RHC were about RHC procedures performed in the ICU or operating room settings. There have been no head-to-head comparisons about the incidence rates of significant arrhythmias or conduction disturbances during RHC performed in the ICU, operating room and CCL settings. The differences of arrhythmias occurring during RHC using different types or sizes (5 French vs 7 French) of balloon tipped catheters was not studied either.

Catheter-induced conduction disturbance during RHC

Right sided conduction disturbances, whether transient or permanent were observed infrequently (less than 1%) during RHC, which rarely resulted in the requirement of permanent pacemakers[ 4 - 7 ]. Damen et al[ 2 ] reported 2 catheter-induced RBBB during 1400 RHCs (0.14%). Ranu et al[ 8 ] retrospectively reviewed charts of 349 patients who underwent RHC and discovered that only 1 patient developed CHB (0.3%) required the removal of the pulmonary artery catheter and insertion of a temporary transvenous pacing wire for 36 hours until the patient recovered normal conduction. CHB could occur during RHC in patients with pre-existing LBBB[ 4 , 9 - 12 ]. In the setting of pre-existing LBBB, Damen found 1 out of 16 patients with LBBB experienced transient CHB requiring temporary pacing (6.3%)[ 2 ]. Morris et al[ 10 ] reported 82 procedures in the ICU setting, during which 7 French balloon-tipped flow directed catheters were used in patients with LBBB, and there was no occurrence of CHB. Based on this, the investigators recommended against routine placement of temporary transvenous pacing wires during RHC in patients with LBBB. The incidence of conduction disturbances during RHC which is performed routinely in the CCL for heart failure, pulmonary hypertension or cardiogenic shock has not been well documented.

Catheter-induced ventricular arrhythmia during RHC

During RHC, both advancing and withdrawing the balloon tipped catheter through the right atrium, right ventricle or pulmonary artery (PA) may cause arrhythmias[ 2 , 13 , 14 ]. Since the initial report of the improved design of the flexible, balloon-tipped, flow-directed catheter for RHC or a PA catheter placement by Swan and Ganz, it has been universally adopted in clinical practice. In Swan et al[ 15 , 16 ]’s initial experience and some subsequent experiences in the CCL, the risk of ventricular arrhythmia was minimal. However, during RHC or PA catheter placement at the bedside in the ICU or OR settings, there were higher rates of various degrees of ventricular arrhythmias such as singlet PVCs, runs of couplets, consecutive PVCs, VT (non-sustained or sustained) and VF, as high as 85% in some reports (Table ​ (Table2). 2 ). All the published reports on ventricular arrhythmias related to RHC were single center studies with either retrospective or prospective designs. There are no uniform definitions in reporting the types of arrhythmias. Table ​ Table2 2 provides the most complete list of published data on the incidence of ventricular arrhythmias during RHC. Most of the observations confirmed that ventricular arrhythmias observed during RHC are generally short-lived and self-limited[ 17 ].

List of studies reported the incidence rate of ventricular arrhythmia during right heart catheterization

Severe life-threatening arrhythmias, such as sustained VT and VF can occur during RHC but are very rare[ 19 ]. Wennevold et al[ 3 ] reported that only 2 VT and 2 VF episodes occurred during more than four thousand RHC (< 0.1%) performed from 1947 to 1963 (before the design of balloon tipped Swan-Ganz catheter). The incidence of sustained VT or VF, requiring anti-arrhythmia treatment either by medication or cardioversion, is relatively low (0.26%[ 19 ], 1%[ 20 ], 1.5%[ 21 ] , 4.7%[ 17 , 22 - 28 ]). Bergmann et al[ 19 ] reported that no episodes of VT and 1 episode of VF requiring defibrillation occurred out of 380 RHCs (0.3%) performed for patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. However, Gwak et al[ 13 ] reported a 2% incidence rates for VT or VF episodes requiring either withdrawal of the catheter or defibrillation, in their prospective observation of 100 PA catheter placements in the OR for liver allograft transplant recipients.

Cardiac arrhythmias during LHC, coronary angiography and intervention

Ventricular arrhythmias during LHC and coronary interventions: Much attention was paid to the occurrence of malignant ventricular arrhythmias – VF, VT and ventricular arrest/asystole (VA) during the early decades of coronary artery angiography (CAG). There were many reports from experienced single centers as well as multicenter registries detailing ventricular arrhythmias. Table ​ Table3 3 provides a comprehensive list of published reports of incidence rates of malignant ventricular arrhythmias during CAG. Gau et al[ 29 ] reported an unusually high incidence rate of VF (12%) in their single center study of 75 cases of selective CAG. Excluding this outlier, the median reported incidence rates of ventricular arrhythmias during diagnostic CAG is 0.9% with a range of 0.1% to 1.7%. Taken together the published data reported total of 163090 cases with 1260 incidences of malignant ventricular arrhythmias that resulted in an accumulated incidence rate of 0.77%. In the period of 1960s, ventricular arrhythmias occurred at the rate of 1.1% in CAG in the reported series (134 incidences in 11747 cases); in the 1970s, the rate was 1.0% (738 events in 73097 cases); in the 1980s, 0.8% (216 events in 26231 cases); and in the 1990s, 0.6% (136 events in 24142 cases). More recently, there were two reports from the same institute in China that included more than 18365 and 27798 diagnostic CAG respectively, using 4 or 5 French catheters. Due to the potential overlap of cases in these two reports, only the later report which included the larger sample size was included in our cumulative calculation. The incidence rate of VF was reported to be 0.1%. The temporal trends show that the incidence rates of malignant ventricular arrhythmias during diagnostic CAG have steadily declined from 1.1% to as low as 0.1% in contemporary practice (Table ​ (Table3). 3 ). Figure ​ Figure1 1 provides a graphic view of the trend of reported incidence rates of VT/VF.

Graphic view of reported incidence rates of ventricular tachycardia / ventricular fibrillation during coronary angiography. Gau et al[ 29 ] reported in 1970, an outlier with high incidence of ventricular fibrillation (VF) in their early experience of 75 cases of coronary angiography (CAG). Excluding the outlier, other reported VF/ventricular tachycardia (VT) incidence rates were consistently low with median 0.9%, (range 0.1% to 1.7%). Total reported CAG cases excluding the 75 cases in Gau et al[ 29 ] were 163015, and total VF/VT cases 1251, with the incidence rate of 0.8%. VF: Ventricular fibrillation; VT: Ventricular tachycardia.

Incidence rate of arrhythmia in coronary angiography and percutaneous coronary interventions

Percutaneous transluminal coronary angioplasty (PTCA) or percutaneous coronary intervention (PCI) has become the most commonly used approach to revascularize obstructive coronary artery disease both in stable ischemic conditions and acute myocardial infarctions. Ventricular arrhythmias are commonly encountered during PCI. In an early study of 1500 PTCA cases, Dorros et al[ 30 ] reported an incidence rate of 1.6% of VF and 0.5% of sustained VT required intervention. Subsequent reports of the rate of ventricular arrhythmias from both single center experiences and registries ranged from 0.84% to 4.3%[ 31 - 36 ]. Addala et al[ 31 ] have so far reported the largest single center cohort, with more than 19000 PTCA cases and 164 events of VF (0.84%). Based on the published data (255 events in 23882 PTCA cases), the cumulative incidence rates of VF/VT during PTCA in patients with stable or unstable angina was calculated to be 1.1%. Mehta et al[ 35 ] and Har et al[ 36 ] both reported a higher incidence of VF during primary PCI for ST-elevation myocardial infarction (STEMI), 4.3% and 4.1% respectively (Table ​ (Table3). 3 ). Available data in the literature suggests that the incidence rates of ventricular arrhythmias during PCI in patients with stable and acute coronary artery disease have been relatively constant in the past two decades of practice. NCDR CathPCI registry ® and ACTION registry ® did not collect information about intra-procedural arrhythmias during diagnostic CAG and PCI until the newest version of data collection form (version 5) for CathPCI registry ® was implemented in July 2018.

Without timely termination, malignant ventricular arrhythmias could be life-threatening. Intrinsic build-in telemetry monitoring by trained staff in CCL has proven to be effective. In the reported series, the episodes of VT/VF during diagnostic LHC and CAG left minimal impact on long term outcomes. Gau et al[ 29 ] reported that all 9 episodes of VF in their first 75 CAG experiences (12% incidence rate) were successfully defibrillated without impacts on outcomes. Others reported the same successful immediate restoration of normal rhythm from intra-procedural VF/VT episodes without adverse sequelae during the hospitalization[ 30 , 31 , 37 - 39 ]. The prognosis of patients with stable coronary artery disease was more governed by the status of CAD and left ventricular dysfunction and other comorbidities, rather than the occurrence of VT/VF during the procedure[ 40 ].

Whether ventricular arrhythmias in the setting of acute myocardial infarctions have an impact on outcomes has been a controversial question. Mehta et al[ 35 ] reported that the occurrence of VT/VF during primary PCI did not influence PCI success, in-hospital or one-year outcomes, compared to patients who did not have intra-procedural ventricular arrhythmias. However, Har et al[ 36 ] recently found that, compared to patients without ventricular arrhythmias, the occurrence of intra-procedural VF/VT requiring cardioversion during primary PCI for STEMI was associated with increased early post-MI mortality (12.0% vs 0.5% in-hospital mortality, and 24.1% vs 3.6% of 30 days mortality); but not late mortality.

Atrial tachy-arrhythmia in LHC and coronary interventions: Bourassa et al[ 37 ] reported a 0.17% atrial tachy-arrhythmia (AF and SVT) in 5250 CAG cases in their single center study. Balloon inflation during PTCA was found to increase P wave dispersions and as well as the maximum duration of P waves[ 41 ]. which may result in increased risk of AF. There are no recent studies reporting atrial tachy-arrhythmias during LHC and coronary interventions.

FFR measurement and intravascular imaging related arrhythmias: Park et al[ 42 ] reported their first intracoronary adenosine-induced AF during FFR measurement. The patient required hospitalization, and amiodarone administration which led to sinus conversion, and a medical regimen for thromboembolic event prophylaxis. More seriously, there were a total of 7 cases of intracoronary adenosine induced VF during FFR have been reported in the literature[ 43 - 45 ]. Various doses (from 96 mcg to 360 mcg and 480 mcg) of intracoronary adenosine boluses were delivered right before the VF occurred. Shah et al[ 45 ] reported the incidence rate of VF during FFR was 0.9% (3 cases in 326 FFR cases). They postulated that the large volume of adenosine/saline solute injection (up to 30 cc/injection) might have contributed to the induction of VF by causing ischemia. By increasing the adenosine concentration and reducing the volume of injection with a similarly high dose of adenosine, Shah reported the avoidance of VF. The overall rate of intracoronary adenosine-induced VT/VF during FFR measurement is unknown. There is no reported case of intravenous adenosine induced VF. Intracoronary papaverine is also used to induce maximum hyperemia in FFR measurement. It was well known that use of intracoronary papaverine during FFR may prolong QT interval and induce polymorphic VT and VF[ 46 - 49 ]. The risk of polymorphic VT (torsade de pointes) and VF has been reported to be around 1.2%-1.3%[ 48 , 50 ].

The potential risk of cardiac arrhythmias, especially malignant ventricular arrhythmias associated with intravascular imaging such as IVUS and OCT, has been reported to be 1.1% (5 out of 468 cases). VF rate was reported in a multicenter evaluation of the safety of OCT[ 51 ]. However, transient chest pain and electrocardiographic changes (QRS widening/ST segment depression/elevation) have been observed in 47.6% cases[ 52 ].

Brady-arrhythmias and conduction disturbances during LHC and coronary angiography: The risk of conduction disturbances is low during procedures performed via femoral artery approach and higher when using a radial artery approach. One study reported the incidence of symptomatic sinus bradycardia in patients undergoing trans-radial coronary angiography to be as high as 4.3%[ 53 ]. In almost all cases, the heart rate returned to normal with adjustment of catheter or atropine administration without residual consequences[ 53 , 54 ]. The etiology of this phenomenon is unclear. Perhaps catheter stimulation or stretch of subclavian, brachiocephalic arteries or ascending aorta may induce a vasovagal reaction.

Arrhythmias during right heart catheterization

Conduction disturbances were recognized during the very early practice of intracardiac catheterization[ 27 ]. It was anticipated that advancing catheters through the ventricle, would irritate the right bundle branch and its fascicular branches and might lead to transient or even permanent injuries. Fortunately the incidence of conduction abnormalities as well as ventricular arrhythmias is low and the long term implications are relatively negligible.

Pre-disposing risk factors associated with the increased incidence of ventricular arrhythmias, in particular the risk of VT or VF requiring intervention during RHC, include myocardial infarctions, septic shock[ 55 ], pre-existing cardiac conditions[ 17 ], use of a guidewire to assist PA catheter advancement[ 56 ], prolonged procedural time and presence of valvular diseases[ 23 , 55 ]. Recent studies suggested that positioning the patient in the head-up and right lateral position while passing right heart catheters would allow the catheter to easily enter the right ventricular outflow tract and thereby, reduce the incidence of severe arrhythmias[ 28 , 57 ]. Intravenous lidocaine administration before the catheter enters the right ventricle for prophylaxis of ventricular arrhythmias was tested, but its use remains controversial[ 58 - 60 ]. Due to the fact that the majority of catheter-induced ventricular arrhythmias are benign, self-limited, and rarely required medical or cardioversion, prophylactic lidocaine is not recommended during RHC.

Arrhythmias during left heart catheterization

The belief that the selective injection of contrast medium into coronary arteries would result in asymmetrical hypoxia, electrical imbalance, and invariantly ventricular arrhythmias was disproved by the pioneer of coronary arteriography, Dr. Sones Jr[ 61 , 62 ]. However, the fear of fatal ventricular arrhythmias related to coronary angiography persists. Due to the proximity of catheters, wires and other equipment to the ventricular walls during LHC, ventricular arrhythmias will unavoidably occur despite the advancement of techniques, reagents and equipment. Direct stimulation with wires and catheters of the ventricular myocardial tissues may disturb local electric activities and introduce myocardial contractions which lead to PVCs in singlets, couples or runs continuously for various lengths. Therefore, advancing equipment into the left ventricular chamber leading to frequent PVCs, non-sustained ventricular tachycardia (NSVT) with cPVCs ≥ 3 beats or ventricular tachycardia (cPVCs ≥ 30 beats) are common, up to 80% in our catheterization laboratory at New York Presbyterian Queens (Shaik et al manuscript in preparation). These ventricular arrhythmias are usually terminated by catheter manipulations (withdrawal, repositioning etc .) without significant impact on hemodynamics. Malignant ventricular arrhythmias, such as sustained VT, VF and ventricular arrest or standstill could occur but are much less common. These malignant ventricular arrhythmias usually cause hemodynamic compromise and require immediate interventions, i.e . chest wall compression, cardioversion and possibly the administration of a pharmacological agent. These malignant ventricular arrhythmias are also the topic of many case reports throughout recent decades. Understanding their potential causes, contributing factors, and approaches to minimize the risk as well as preparing to manage them when they occur are one of the core subjects of training in the interventional cardiology community.

Causes and contributing factors of ventricular arrhythmias during LHC and approaches to minimize the risk

The more than 10 folds decrease in incidence rate of malignant ventricular arrhythmias during CAG and LHC is the result of half a century’s clinical and translations research. It is generally accepted that ischemic changes of myocardium, toxicities of contrast medium[ 63 - 66 ], and mechanical stimulations of myocardial tissue by catheter and wires, contribute to the occurrence of ventricular arrhythmias. Individual patients’ vulnerability or susceptibilities to ventricular arrhythmias, often influenced by electrolyte derangement, pre-existing prolongation of QT interval, small caliber coronary arteries, or the severities and acuities of coronary artery disease, also play important roles. Furthermore, the operators’ experience and approach in performing the LHC and coronary intervention also dictate outcomes (Table ​ (Table4 4 ).

Known risk factors for ventricular tachycardia / ventricular fibrillation during coronary angiography and percutaneous coronary intervention and approaches to mitigate the risk

CM: Contrast medium; VT: Ventricular tachycardia; VF: Ventricular fibrillation; LV: Left ventricular; CAG: Coronary angiography; CAD: Coronary artery disease; RCA: Right coronary artery; PCI: Percutaneous coronary intervention; EF: Ejection fraction.

Atrial tachy-arrhythmia in LHC and coronary interventions

Contrary to RHC, LHC is performed via a retrograde approach. There is no direct contact of instruments with atrial structures. Direct stimulation of the atrium causing arrhythmia is rare during LHC and coronary interventions. Thus, the findings of our literature review are not surprising.

FFR measurement and intravascular imaging related arrhythmias during LHC and coronary interventions

In symptomatic patients with moderate coronary artery stenosis, guidelines supported by robust clinical evidence recommend the use of FFR to guide the clinical decision making process[ 67 ]. The risk of arrhythmias during FFR measurement involves instrumentation of the coronary arteries with guidewires, catheters and contrast medium, as well as the pro-arrhythmic effects[ 68 ] of adenosine, which is the most commonly used agent to induce maximum hyperemia[ 69 ]. Intravenous infusion of adenosine at 140 mcg/kg/min or intracoronary bolus injection at the doses of 60 mcg, 120 mcg, up to 480mcg, are generally safe and well tolerated, largely owing to its very short half-life. Adenosine induced transient sinus bradycardia, AV block, and sinus tachycardia are common and expected physiologic effects on the heart rhythm. Adenosine-induced arrhythmias and conduction disturbance are short-lived and self-limited without the need of special treatment. The current gold standard for FFR studies is to use intravenous adenosine to induce hyperemia, especially when taking into consideration the reported risk of severe ventricular arrhythmias which using intracoronary adenosine and papaverine. However, head-to-head safety data is not available.

Because OCT involves high volume contrast injections to disperse blood components during image acquisition the incidence of ventricular arrhythmias is higher. This may cause chest pain, electrocardiographic changes and even ventricular arrhythmias – all three of which have been reported in the literature. There are no particular concerns regarding IVUS studies causing ventricular arrhythmias.

Brady-arrhythmias and conduction disturbances during LHC and coronary angiography

Brady-arrhythmias have been recognized since the very early experiences and are relatively common during LHC and coronary angiography[ 70 ].Direct toxicity of contrast medium and stimulation of chemoreceptors, other vasovagal reactions induced by pain and anxiety, etc . were the proposed mechanisms of these arrhythmias[ 70 - 72 ].Lately, with the growing popularities of trans-radial catheterization, coiling of the catheters and direct stimulation of the aortic arch and carotid sinus receptors was also noted to cause sinus bradycardia[ 54 ].

An infrequent yet significant conduction disturbance associated with LHC and CAG is LBBB and/or CHB. As opposed to the right bundle, the trunk of the left bundle is generally short and immediately divides into two fascicles. The left bundle branch is also broadly distributed over the left septal surface in a diffuse fanlike structure. To some extent, these anatomic features of the left bundle protect it from mechanical damage during catheter instrumentation of the left ventricle. Some patients, however, may have anatomic variations, which include a left bundle that extends undivided for 20 mm or more, making the left bundle vulnerable. Shimamoto et al[ 73 ] reported 3 patients, without any known conduction abnormalities or evidence of infarction prior to LHC, who developed LBBB, without a change in heart rate during coronary angiography. Of these patients, only one eventually developed a permanent LBBB and none had significant complications. The recognition of the possibility of developing LBBB is particularly important when patients have pre-existing right bundle branch and/or fascicular blocks, which could potentially require permanent pacemaker implantation if persistent CHB occurs[ 74 - 76 ]. Furthermore, the His bundle travels through the membranous septum in immediate proximity to the posterior sinus of Valsalva and runs just under the left ventricular endocardium. It is thus, anatomically vulnerable to mechanical trauma during LHC and CAG. A single touch of these structures by the catheter tip may cause intra-His bundle injury resulting in CHB[ 75 , 77 - 80 ].

Understanding the risk factors for development of brady-arrhythmias and conduction disturbances during LHC and CAG helps the operator to be prepared should these arrhythmias occur and compromise hemodynamics, which will require either administration of atropine and other drugs, and/or emergent transvenous pacing. However, given the low incidence as well as relatively rapid recovery in most of the cases, prophylactic temporary transvenous pacing as performed earlier in practice[ 79 ] is no longer recommended. In recent years, there has been a growing interest in using coronary catheters and guidewires for left ventricular pacing in order to reduce resource utilization and avoid the risks of transvenous wire placement[ 81 - 84 ].

In conclusion, diagnostic RHC, LHC, CAG, and coronary interventions are the most commonly performed invasive cardiac procedures. This systematic literature review demonstrated a 0.14%-0.3% incidence of transient RBBB during RHC in normal individuals, with a significantly higher risk of CHB (up to 6.3%) requiring temporary or permanent pacing for individuals with pre-existing LBBB. Isolated PVCs or non-sustained VT which do not require specific treatment are common (approximately 20% incidence rate in most of the reports) during RHC. Potentially life-threatening ventricular arrhythmias (sustained VT and/or VF) requiring either withdrawal of catheter or cardioversion also occur but at much lower rates (1%-1.3%). The incidence rate of diagnostic LHC and CAG causing arrhythmias has reduced 10 fold in the last half century from 1.1% to 0.1% (in modern era) due to an improved procedural techniques, better training, improved contrast medium, and equipment. Coronary interventions as well as hemodynamic assessment with FFR and intracoronary imaging (especially OCT) continue to carry an increased risk of introducing malignant arrhythmias with up to 1% incidence rate of VF requiring shocks. Rigorous and constant monitoring, and readiness to intervene are essential for the modern cardiac catheterization facility.

ARTICLE HIGHLIGHTS

Research background.

Cardiac Catheterization is one of the most commonly performed procedures in the modern health care system. Given the nature of intracardiac and intracoronary manipulation of catheters during the procedure, arrhythmias are common, and potentially consequential. Understanding the incidence, risk factors and strategies to mitigate the risk bears clinical significance.

Research motivation

There are sporadic reports on the topics of intra-procedural arrhythmias during cardiac catheterization. We systematically reviewed published literature, analyzed the incidence rate, temporary trends, and predictors of atrial and ventricular arrhythmias during left and right heart cardiac catheterization. We also discussed factors and approaches to reduce arrhythmias and improve the safety of the procedures.

Research objectives

The goal of this study is to provide a comprehensive overview of the incidence rates and impact on short- and long-term outcomes of arrhythmias during cardiac catheterization, as well as understand approaches to minimize the risk of malignant arrhythmias during cardiac catheterization.

Research methods

We systematically searched PubMed, EMBASE and Cochrane databases with a combination of comprehensive terms related to cardiac catheterization procedures and various cardiac arrhythmias, then carefully reviewed and synthesized the data by types of procedure and arrhythmias.

Research results

We found a 0.14-0.3% incidence of transient right bundle branch block during right heart catheterization (RHC) in normal individuals, and a significantly higher risk of complete heart block (up to 6.3%) requiring temporary or permanent pacing for individuals with pre-existing left bundle branch block (LBBB). Isolated premature ventricular contraction or non-sustained ventricular tachycardia (VT) which do not require specific treatment are common (approximately 20% incidence rate) during RHC. Potentially life-threatening ventricular arrhythmias (sustained VT and/or ventricular fibrillation) requiring either withdrawal of catheter or cardioversion also occur but at lower rates (1.0%-1.3%). The incidence rate of diagnostic left heart catheterization and coronary angiography causing arrhythmias has significantly reduced from 1.1% to 0.1% in the last half century. However, invasive coronary intervention and hemodynamic assessment including optical computed tomography and fractional flow reserve continue to possess a significantly higher risk.

Research conclusions

Cardiac arrhythmias are common during cardiac catheterization. While the majority of arrhythmias are benign and self-limited, complete heart block in the presence of pre-existing LBBB and ventricular tachycardia during RHC could be consequential requiring interventions. As the improvement of reagents, equipment and techniques, the incidence rate of serious arrhythmias such as ventricular tachycardia/fibrillation during LHC has significantly decreased, but it continues to require constant intra-procedural monitoring and readiness to intervene.

Research perspectives

As cardiac catheterization procedure continues to serve as essential diagnostic and therapeutic tool for patients, intra-procedural cardiac arrhythmias occur at relatively low incidence rates. Understanding the types of arrhythmias, associated risk factors and the strategies to monitor and mitigate the risk continue to be essential for patient safety and procedure success. It continues to require close surveillance and exploration of best practice to minimize the risk.

ACKNOWLEDGEMENTS

The authors thank the staff in the cardiac catheterization laboratory of New York Presbyterian Queens hospital for their supports for the relevant research on cardiac arrhythmia during cardiac catheterization. We also wanted to thank the reviewers and editors for the constructive comments which helped improve the manuscript to current form.

Conflict-of-interest statement: The authors have no conflicts of interest to declare.

PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared, revised and presented according to the PRISMA 2009 Checklist.

Manuscript source: Invited manuscript

Peer-review started: February 26, 2020

First decision: April 25, 2020

Article in press: May 26, 2020

Specialty type: Cardiac and cardiovascular systems

Country/Territory of origin: United States

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): 0

Grade C (Good): C

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Avanzas P S-Editor: Yang Y L-Editor: A E-Editor: Qi LL

Contributor Information

Fatima A Shaik, Division of Cardiology, New York Presbyterian Queens Hospital, Flushing, NY 11355, United States.

David J Slotwiner, Division of Cardiology, New York Presbyterian Queens Hospital, Flushing, NY 11355, United States.

Gregory M Gustafson, Division of Cardiology, New York Presbyterian Queens Hospital, Flushing, NY 11355, United States.

Xuming Dai, Division of Cardiology, New York Presbyterian Queens Hospital, Flushing, NY 11355, United States. gro.pyn@2009dux .

Uruguayan soccer player dies in hospital days after collapsing during game

Hospital albert einstein in brazil issued a statement saying izquierdo died following “cardiorespiratory arrest associated with his cardiac arrhythmia.” , by mauricio savarse | the associated press • published august 28, 2024 • updated on august 28, 2024 at 12:06 pm.

Uruguayan soccer player Juan Izquierdo died Tuesday at a hospital in Brazil five days after collapsing during a game at Sao Paulo. He was 27.

Hospital Albert Einstein in Sao Paulo said in a statement that the Nacional defender died at 9:38 p.m. local time following “cardiorespiratory arrest associated with his cardiac arrhythmia.”

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Izquierdo collapsed last Thursday in a Copa Libertadores soccer match between Nacional and Sao Paulo at the Brazilian city’s Morumbi Stadium.

Uruguay's air force said one of its planes will transport his coffin to Montevideo later on Wednesday.

Izquierdo's wife, Selena, shared a message on Izquierdo’s social media channels to “say goodbye to my half, the love of my life.” They have two children — the youngest, a boy, was born earlier in August.

“For many, Juan Izquierdo, my Juanma, my best friend, my husband, the father of my children, my unconditional partner. Today a part of me dies with you,” she said.

Mateo Antoni, a teammate of Izquierdo’s, said the defender “helped, advised, mentored, demanded, insulted, hugged and laughed” with him.

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“I can’t describe how great you were with me,” he said in a letter. “What remains with me for all my life is that I know that I will always watch your back because I know you will be watching mine.”

The Uruguayan club posted a statement  on social media saying Izquierdo’s death is felt “in deep pain and impact in our hearts” and “all Nacional is in grief for his irreplaceable loss.”

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South American soccer’s governing body also posted a tribute . CONMEBOL president Alejandro Domínguez said he’s “deeply sorry about the early departure of Juan Izquierdo.

“South American soccer is in mourning,” he said. Other federations, including Uruguay, Brazil and Argentina, also expressed their condolences.

Doctors at the hospital said earlier this week that Izquierdo was put into neurological critical care because of increased intracranial pressure. He had been on a ventilator since Sunday.

Uruguayan national team players were among those expressing their condolences.

“Pain, sadness, it is hard to explain,” Inter Miami striker Luis Suárez said. “May he rest in peace. I wish a lot of strength for his family and friends.”

Uruguay’s first- and second-division soccer leagues were postponed  last weekend due to concerns over Izquierdo’s health. Sao Paulo players wore a shirt in support of the Uruguayan footballer before the team’s 2-1 Brazilian league win against Vitoria on Sunday.

The Brazilian club also posted a message after Izquierdo's death.

“We had days of prayers, union and hope, and today we are in deep sadness with the news of the death of Juan Izquierdo,” Sao Paulo's club statement said. “Our condolences to family, friends, teammates, Nacional fans and all the Uruguayan people in this moment of grief.”

Izquierdo’s professional career began in 2018 at local club Cerro. He joined Peñarol the following year, but didn’t get much playing time.

“Peñarol is deeply sorry about the passing of Juan Manuel Izquierdo. We express our heartfelt condolences and we embrace his family, his friends and Nacional in this moment of so much pain," Peñarol said in its social media channels.

After leaving Peñarol, Izquierdo moved to Montevideo Wanderers.

His athletic form and sharp tackles caught the attention of Mexico’s San Luís in 2021, but he quickly returned to the Wanderers. Izquierdo was signed by Nacional in 2022, played one match and then was transferred to the local Liverpool club.

The defender was one of Liverpool’s best players in the campaign that led to a Uruguayan league title in 2023, the club’s first in more than a century.

Izquierdo returned to Nacional this year and was vying for a position in the starting lineup with veteran Sebastián Coates, who played for Uruguay’s national team. He played 23 matches this year and scored one goal.

Almost two decades ago, Sao Caetano defender Serginho died hours after collapsing at Morumbi Stadium during a Brazilian league match against Sao Paulo. Doctors tried to resuscitate him on the pitch, as tens of thousands of fans watched in shock and players wept and prayed on the sidelines.

Serginho's death forced Brazilian soccer executives to change health protocols to allow defibrillators in every stadium. Doctors used a defibrillator on Izquierdo as he was rushed to the hospital.

“Such sadness, 20 years later,” former Sao Caetano player Anderson Lima said on Instagram. “May God comfort his family in this sad moment.”

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Uruguayan soccer player, 27, dies days after collapsing on field during match

Izquierdo collapsed during a match last week.

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Juan Izquierdo, a Uruguayan soccer player who played for Nacional, died on Tuesday days after he collapsed during a Copa Libertadores match in Brazil. He was 27.

Izquierdo died at Hospital Albert Einstein in Sao Paulo following "cardiorespiratory arrest associated with his cardiac arrhythmia ," according to officials.

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Juan Izquierdo of Uruguay's Liverpool plays in a Copa Libertadores match against Argentinos Juniors in Montevideo, Uruguay, May 3, 2023. (AP Photo/Matilde Campodonico)

Doctors said earlier in the week he was put into neurological critical care because of increased intracranial pressure. He had been on a ventilator since Sunday.

He collapsed last Thursday during Nacional’s match against Sao Paulo.

"For many, Juan Izquierdo, my Juanma, my best friend, my husband, the father of my children, my unconditional partner. Today a part of me dies with you," Izquierdo’s wife, Selena, wrote on the player’s social media channels.

She shared the message to "say goodbye to my half, the love of my life."

Izquierdo’s teammate, Mateo Antoni, remembered him as a mentor and a friend.

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Juan Manuel Izquierdo of Uruguay's Liverpool, left, controls the ball under pressure from Julio Joao Ortiz of Ecuador's Independiente del Valle in Montevideo, Uruguay, May 24, 2023. (AP Photo/Matilde Campodonico, File)

"I can’t describe how great you were with me," he said in a letter. "What remains with me for all my life is that I know that I will always watch your back because I know you will be watching mine."

Izquierdo started his professional career with Cerro of the Uruguayan Primera Division. But he didn’t stay long. He bounced around the league from Penarol to Wanderers and later to Nacional and Liverpool. He played four matches for Atletico in Liga MX in Mexico .

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He re-joined Nacional in 2024 after 27 matches at Liverpool, helping the team to a Uruguayan league title in 2023. He started 13 of the 14 games he appeared in.

The Associated Press contributed to this report.

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Ryan Gaydos is a senior editor for Fox News Digital.

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